# MECHANISMS OF SURGICAL ADJUVANT INTRAVESICAL BCG

> **NIH NIH R01** · JEWISH HOSPITAL OF SAINT LOUIS · 1990 · $179,391

## Abstract

Bacille Calmette-Guerin is the treatment of choice for superficial bladder
tumors.  Prospective randomized clinical trials have shown that the
efficacy of intravesical BCG as an adjuvant to surgery is superior to
surgery alone or adjuvant chemotherapy.  The mechanisms by which BCG
mediates antitumor activity are not known.  The importance of understanding
the mechanisms of action of intravesical BCG could be far-reaching and
could provide a basis for better selection of bladder cancer patients for
therapy, improve monitoring of patient progress to therapy and could
provide a basis for developing immunotherapy protocols for other forms of
cancer.  Furthermore, a clear understanding of the mechanisms could lead to
effective therapy without the need for treating with a viable, potentially
infective, bacterium.  Data from clinical trials on bladder cancer patients
as well as studies on animal tumor models suggest that inhibition of tumor
growth is closely associated with BCG-induced modulation of the immune
response.  The data suggest that intravesical BCG attaches to the bladder
wall via a fibronectin bridge.  Fibronectin attachment appears to be a
requisite first step in the initiation of the immune response to BCG.  The
subsequent development of a T cell dependent immune response is required
for antitumor activity.  Neither the responding T cell subset nor the
actual tumoricidal mechanism are known.  To more clearly understand the
effector mechanisms, a mouse bladder tumor model in which tumors are
implanted directly into bladders has been adapted for the study of
intravesical BCG therapy.  Using this model, the immunological responses
required for inhibition of bladder tumor growth will be studied.  Adoptive
transfer of T lymphocyte subsets will be performed to identify the
population required for antitumor activity.  The antigens recognized will
be determined and clones T lymphocyte cultures will be established.
Effector function of fractionated spleen T cells and cloned T cell lines
will be determined and in vivo antitumor activity of each will be
established.

Factors influencing the initiation of the immune response will be
established including functional analysis of antigen presenting cells and
the modulatory effects of fibronectin on the initiation of the response.
Other effector functions which may be important to antitumor activity
include monokine production, non specific cell-mediated mechanisms and
antibody production.

## Key facts

- **NIH application ID:** 3175880
- **Project number:** 5R01CA037926-07
- **Recipient organization:** JEWISH HOSPITAL OF SAINT LOUIS
- **Principal Investigator:** Timothy L. Ratliff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $179,391
- **Award type:** 5
- **Project period:** 1984-05-01 → 1992-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3175880

## Citation

> US National Institutes of Health, RePORTER application 3175880, MECHANISMS OF SURGICAL ADJUVANT INTRAVESICAL BCG (5R01CA037926-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3175880. Licensed CC0.

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